1. Field of the Invention
The present invention concerns detection of response to nociceptive pain. This invention particularly concerns an automated model for screening anti-nociceptive agents by detecting and measuring a flinch response in an animal whose extremity has been subjected to an irritant such as formalin.
2. Description of the Prior Art
The escape response or agitation evoked by a transient, strong stimulus attests to there being a close relationship between stimulus intensity, peripheral afferent discharge and magnitude of the pain state as defined by response latency and magnitude. There are situations, however, in which the magnitude of the response to pain may exceed what would normally be anticipated given the magnitude of the physical stimulus and the afferent traffic generated by that stimulus (31, 45, 47). These situations are loosely considered as reflecting a state of hyperalgesia, possibly arising from sensitization of the peripheral terminal and/or a central facilitation.
Several preclinical models have been developed that may reflect the significance played by such facilitation on behavior. The common characteristic found in these models is the injury that is induced and its causing of the sensory axon to produce a persistent discharge. A frequently used method of producing injury in the rat is the subcutaneous injection of a small volume of irritant such as formalin into its hind paw. Typically, after the formalin injection, the rat displays a biphasic (Phase I and Phase II) incidence of flinching (rapid paw shaking) and licking of the injected paw (18, 42, 43). The behavioral syndrome produced by the injection of formalin into the paw has been widely used to define the pharmacology of systems that regulate facilitated processing. The “formalin test” has evolved into a widely used tool in the screening of analgesic and anti-hyperalgesic drugs (45).
An important limitation of this behavioral model is its labor-intensive nature regarding data collection and the time required to train observers in its reliable implementation. Several automated systems have been proposed to facilitate data collection. One approach has been to employ strain gauges to measure mass movements of a rat in a confined cylindrical cage (21). A second model involves a video system that employs a pattern recognition algorithm (22). Though of merit, these approaches are limited in that each only indirectly measure movement of the injected paw. Therefore, there is a need for an approach that directly measures movement.
This invention addresses this limitation by presenting a system that assesses only the movement of the injected paw. As described below, this approach involves placing a metal band on the injected paw and detecting the movement of that band with a localized low strength sinusoidal electromagnetic field.